Micro-fluidic device

ABSTRACT

Embodiments described herein provide micro-fluidic systems and devices for use in performing various diagnostic and analytical tests. According to one embodiment, the micro-fluidic device includes a sample chamber for receiving a sample, and a reaction chamber for performing a chemical reaction. A bubble jet pump is structured on the device to control delivery of a fluid from the sample chamber to the reaction chamber. The pump is fluidically coupled to one or more chambers of the device using a fluidic channel such as a capillary. A valve may be coupled to one or more chambers to control flow into and out of those chambers. Also, a sensor may be positioned in one or more of the chambers, such as the reactant chamber, for sensing a property of the fluid within the chamber as well as the presence of a chemical within the chamber.

RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.14/619,791 entitled MICRO-FLUIDIC DEVICE, filed Feb. 11, 2015, which isa Continuation of U.S. patent application Ser. No. 14/224,548 entitledMICRO-FLUIDIC DEVICE, filed Mar. 25, 2014, and issued as U.S. Pat. No.8,980,199, on Mar. 17, 2015, which is a Continuation of U.S. patentapplication Ser. No. 13/858,678 entitled MICRO-FLUIDIC DEVICE, filedApr. 8, 2013, and issued as U.S. Pat. No. 8,709,357 on Apr. 29, 2014,which is a Continuation of U.S. patent application Ser. No. 13/448,235entitled MICRO-FLUIDIC DEVICE, filed Apr. 16, 2012 and issued as U.S.Pat. No. 8,414,849 on Apr. 9, 2013, which is a Continuation of U.S.patent application Ser. No. 12/541,797 entitled MICRO-FLUIDIC DEVICE,filed Aug. 14, 2009 and issued as U.S. Pat. No. 8,158,082 on Apr. 17,2012, which claims the benefit of Provisional U.S. Patent ApplicationNo. 61/093,283, entitled MICRO-FLUIDIC DEVICE, filed Aug. 29, 2008; allof the aforementioned priority applications being hereby incorporated byreference in their respective entirety for all purposes.

BACKGROUND Field of the Invention

Embodiments described herein relate to micro-fluidic devices. Morespecifically, embodiments relate to micro-fluidic devices having abubble jet pump.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view illustrating an embodiment of amicro-fluidic device including a bubble jet based pump.

FIG. 2 is a schematic view illustrating an embodiment of a micro-fluidiccircuit including a bubble jet based pump.

FIG. 3 is a schematic view illustrating another embodiment of amicro-fluidic circuit including a bubble jet based pump, controller andother components.

FIG. 4 is a schematic view illustrating another embodiment of amicro-fluidic circuit including a bubble jet based pump that isconfigured to be coupled to an external analytical device.

DETAILED DESCRIPTION

Embodiments described herein provide micro-fluidic systems and devicesfor use in performing various diagnostic tests. Many embodiments employa bubble jet based pump as a mechanism for precisely controlling theflow of fluids within the device, including the introduction of fluidsinto one or more reaction chambers disposed within the device. Suchembodiments allow for the precise control of: (i) the introduction of asample fluid into a reaction chamber, and/or (ii) sequenced or timedintroduction of one or more reactants for the sample fluid to allow fora chemical reaction to occur in the chamber. Such chemical reactions canbe used to perform medical diagnostic tests or assays, including thoseused for colorometric assays and immunoassays including enzyme-linkedimmunosorbent assay (ELISA) and other immuno-based assays known in theart.

Embodiments described herein provide micro-fluidic systems and devicesfor use in performing various diagnostic tests. Embodiments of thedevice can include one or more chambers to enable receiving and reactionof fluid samples used in performing a diagnostic test. According to oneembodiment, the micro-fluidic device includes a sample chamber forreceiving a sample, and a reaction chamber for performing a chemicalreaction. A bubble jet pump is structured on the device to controldelivery of a fluid from the sample chamber to the reaction chamber. Thepump is fluidically coupled to one or more chambers of the device usinga fluidic channel such as a capillary. A valve may also be coupled toone or more chambers to control flow into and out of those chambers.Additionally, a sensor may be positioned in one or more of the chambers,such as the reactant chamber, for sensing a property of the fluid withinthe chamber as well as the presence of a chemical within the chamber.

Further details of these and other embodiments of micro-fluidic systemsand devices are described more fully below with reference to theattached figures.

Referring now to FIGS. 1-4, an embodiment of a micro-fluidic device 10can include one or more micro-fluidic features 11 for performing one ormore functions on the device. Such features 11 can include fluidicchannels 20, ports 22, a sample chamber 30 (which may containing a testsample 31), one or more reactant chambers 40 containing one or morereactants 41, 42, 43, a pump 70 and a collection chamber 80 forcollection of fluid 81. Fluidic channels 20 provide a pathway on themicro-fluidic device 10 in which a fluid can flow between or amongvarious chambers, pumps, ports and other features 11 on themicro-fluidic device 10. One or more features 11 can be arranged to forma micro-fluidic circuit 15. FIG. 2 illustrates an embodiment of amicro-fluidic circuit 15. Other arrangements or configurations formicro-fluidic circuits 15 may also be provided.

Micro-fluidic device 10, including one or more features 11, can beformed on a variety of substrates including silicon as well as polymerbased substrates using etching and/or lithographic processes known inthe art. Suitable polymers include elastomeric polymers such assilicone. Typically, micro-fluidic device 10 will comprise amicro-fluidic chip 10C that is configured to engage or otherwise becoupled to one or more medical diagnostic or analytical instruments.However, other micro-fluidic devices are also contemplated. For example,micro-fluidic device 10 can comprise a micro-fluidic column or otherseparation device that mates with a medical diagnostic or analyticalinstrument. Alternatively, micro-fluidic device 10 can be a stand alonedevice such as a lab-on-a-chip that needs no external connections andcan even include its own power source, such as a miniature lithiumbattery (e.g., a button battery) or other miniature battery.

Ports 22 are coupled to channels 20 and provide a pathway for the flowof fluid in and/or out of micro-fluidic device 10. Typically,micro-fluidic device 10 will include at least one inlet and outlet port22, but can have one or the other, or none. Multiple inlet and outletports 22 are also contemplated to allow for the inflow and outflow ofmultiple fluids and/or parallel fluid flow of the same or differentfluids.

In one embodiment, channels 20 can include one or more valves 50 tocontrol the flow of fluid into and out of various chambers and otherfeatures 11 on the micro-fluidic device 10, as well as the direction 21of fluid flow. Valves 50 can also be positioned at or integral tochambers 30, 40, 60 and 80, as well as pump 70. They can also bepositioned at ports 22. In various embodiments, valves 50 can compriseone or more of an electronically, pneumatically, pressure ormagnetically actuatable valve. Valves 50 can be one-way or two-way, andcan be controlled electronically by means of a controller 90, such as amicroprocessor. In one embodiment, a valve 50 can comprise a pressureoperated check valve. The cracking pressure of the valve 50 can beselected for the particular pressure generated by pump 70.

In many embodiments, pump 70 comprises a bubble jet pump device 71. Inone embodiment, the bubble jet pump device 71 includes a heating element72 that is used to controllably heat liquid within the pump chamber 73to form a vapor bubble 74 which forces out a jet of a fixed volume ofliquid 75. Bubble jet pump device 71 can be similar to ink jet/bubblejet devices used in ink jet printers. However, according to one or moreembodiments, bubble jet pump device 71 is adapted to function as avacuum pump to controllably pull in a selected volume of fluid intoreaction chamber 60 or other feature 11, rather than eject or depositfluid onto a surface. Heating element 72 can comprise aresistive/joulean heating element, but other heating elements are alsocontemplated including, RF, microwave, acoustic, infrared and gaselements. The ejected volume of liquid 75 (also known as drop size 75)creates vacuum pressure which pulls a fixed volume of fluid 76 fromreaction chamber 60 and in turn, a fluid volume 77 drawn into thechamber from either sample chamber 30, reactant chamber 40 or otherfeature 11. The volume of drawn fluid 77 can be controlled bycontrolling the drop size 75. The drop size 75 can be controlled byusing various methods known in the bubble jet arts including controllingone or more of the power, duration and duty cycle of heating fromheating element 72. Other methods of controlling drop size 75 are alsocontemplated. For example, drop size 75 can be controlled through use ofcontrol valve 50 alone or in combination with other methods describedabove.

In various embodiments, heating element 72 can include an overlyinghydrogel or other water containing polymer layer such that the vaporbubble 74 is derived from a phase change of water contained in thehydrogel layer rather than from fluid within chamber 73. In this way,fluid within chamber 73 is thermally shielded from direct contact withheating element 72 while still allowing for the ejection of fluid frompump chamber 73 and pump 71. The hydrogel layer can be configured tohave a sufficient amount of trapped water or an aqueous based solutionto allow for multiple firings of pump 71.

In the embodiment shown in FIG. 2, a single bubble jet pump 71 is shownto be coupled with reaction chamber 60. However in various embodiments,multiple bubble jet pumps 71 may be used. For example, each reactantchamber 40 can have its own bubble jet pump 71 in order tosimultaneously (or close to simultaneously) enable or cause mixing oftest sample 31 and reactants 41 in the reaction chamber 60. Othercombination for connecting bubble jet pumps 71 to one or more features11 are also contemplated. For example, bubble jet pump 71 can be coupledto an inlet port 22 to pull a sample fluid 31 into micro-fluidic device10 from an external source.

In many embodiments, bubble jet pump(s) 71 including heating element 72are electronically coupled to a controller 90, which can either be adevice resident controller 91 or an external controller 92 or both.Heating element 72 and/or controller 91 can also be configured to enablewireless communication capabilities with an external controller ormonitoring device 92, including RF communications, such as provided bystandards such as BLUE TOOTH or WIRELESS USB. Controller 90 can comprisea microprocessor, a state device or analog control circuit. Controller90 can also be coupled to one or more control valves 50 to control thesequence and timing of fluid delivery from sample chamber 30 andreactant chambers 40.

In particular embodiments, bubble jet pump 71 is configured to pull acontrolled volume of fluid 77 into reaction chamber 60 from one or moreof sample chamber 30, reactant chamber(s) 40 or other device feature 11.The amount of fluid drawn is selectable using techniques described aboveor other techniques known in the art. In various embodiments, the volumeof drawn fluid 76 can be controlled using controller 90. Differentcontrolled volumes 77 can be selected from sample chamber 30 and eachreactant chamber 40. Controller 90 can contain one or more algorithms 93which include a group and sequence of selected volumes 77 that arepulled from chambers 30 and 40 or other feature 11 depending on ananalytical test to be performed within reaction chamber 60. Algorithms93 can also include a sequence of valve operations for opening andclosing control valves 50 to control the sequence of fluid deliveredfrom chambers 30, 40 or other feature 11. Algorithms 93 can bepreprogrammed on controller 90 or can also be signaled to controller 90from an external controller using RF or other signaling method. Invarious embodiments, resident controller 91 can incorporate an RF ID tagor like device 94 for communication with external controller 92. RF IDtag 94 can also be a separate device that is positioned at selectablelocation on device 10.

In one embodiment, reaction chamber 60 is configured to allow for themixing of sample 31 with one or more chemical reactants 41 so as to havea chemical reaction take place in the chamber to produce a productsolution 61. Product solution 61 can have a particular property, such asa color, pH, etc., which allows for the detection and/or quantificationof a particular analyte 32 in sample 30 (for example, a serum antibodysuch as the HIV antibody, or an analyte such as blood glucose,cholesterol (e.g., HDL, LDL), lipids, or a particular drug). In anotherembodiment, reactants 41 and reaction chamber 60 can be configured forperforming a hematocrit or blood iron concentration test usinganalytical methods known in the art (e.g., a serum ferritin test asknown in the art). Accordingly, in various embodiments, reaction chamber60 can include one or more sensors 100 to allow for thedetection/quantification of product solution 61, including solutions formeasuring hematocrit and/or blood iron. The sensor 100 can be an opticalsensor including a detector and emitter for doing various spectrometricmeasurements of solution 61. The emitter can use wavelengths configuredto produce fluorescence in solution 61 (for example, to allow for thedetection of an antibody containing a fluorescent compound or thepresence of the heme molecule in blood). The emitter and detector canalso be configured for performing various reflectance and absorbancemeasurements known in the art for detecting colorometric reactions insolution 61, such as those used for the detection of blood glucose. Insuch embodiments, the emitter and detector can be offset a selectabledistance and angle to allow for reflectance and/or absorbancemeasurement. In other embodiments, sensor 100 can be a pH sensor,temperature sensor, gas (e.g., O₂) sensor, flow sensor or other sensorknown in the sensor art. Multiple sensors 100 can also be employed andplaced in multiple locations in reaction chamber 60, reactant chamber 40or in other features 11 to allow for multiple measurements in multiplelocations on device 10. Embodiments having multiple sensors 100 canallow for improved real time control of the tests performed by device10.

In one embodiment, sensor 100 is configured to send a signal or input110 to controller 90 (e.g., either controller 91 or 92), which can beused for detection and/or quantification of analyte 32. In addition,Signal 110 can be used for monitoring the progress of the chemicalreaction in reaction chamber 60. Signal 110 can also be used bycontroller 90 to control the sequence of the introduction of sample,reactant and other fluids into and out of reaction chamber 60 or otherfeatures 11. In particular embodiments, signal 110 is used to controlthe actuation of bubble jet pump(s) 71.

In other embodiments, micro-fluidic device 10 can be configured to becoupled to an external analytical device 120, such as aspectrophotometer, which generates a detection peak or waveformcharacteristic 130 of a particular analyte 32. Coupling the externaldevice 120 to device 10 can be achieved through the use of port 22and/or valve 50.

Embodiments of the micro-fluidic device 10 can be used in conjunctionwith a variety of systems. These systems can include a variety ofmicro-fluidic systems including, without limitation, micro-fluidicchips, micro-fluidic lab-on-chip devices, ELISA devices, electrophoresisdevices, chromatography devices, micro-arrays, micro-fluidic columns andother like devices.

In various embodiments of methods of using device 10, one or more ofsample chamber 30, reaction chamber 60 and connecting channels 20 caninitially contain air. Also, reactant chambers 40 can be pre-primed withreactants 41, or reactants 41 can be added to the reactant chambers 40(e.g., by using an automated device). The user can also add sample 31 tosample chamber 30 by using a pipette or a similar device, or enablesample 31 to be added to the sample chamber 30 by using an automateddevice. When pump 71 is first actuated, it serves to evacuate all of theair from the connecting channel 20 and reaction chamber 60, and draw ina fixed amount of fluid sample 31 from the sample chamber 30. Thisallows reaction chamber 60 to be kept in a dry condition (in suchembodiments, reaction chamber 60 may contain one or more dry reactants40). A control valve 50 connecting the reaction chamber 60 with thesample chamber 30 can then be closed, and another control valve 50 canbe opened to connect the reaction chamber 60 to a reactant chamber 40that contains a reservoir of chemical reactant 41 (such as an antibodyor enzyme). The pump 70 is then actuated again, thereby drawing in afixed amount of reactant 41. This process can then be continued with oneor more other reactant reservoir chambers with the volume and timesequence of each added reactant being controlled via the bubble jet pumpand a signal from the controller. Different volumes can be selected fordifferent reactants with a fixed time interval between additions toallow for mixing and subsequent chemical reaction in the reactionchamber.

The reaction chamber 60 can be configured to perform various diagnostictests such as ELISA (or other antibody based test) or a blood ironconcentration test, such as a serum ferritin test. Also, the reactionchamber 60 can include various optical emitters and detectors (such aphotomultiplier tube) to detect the presence of one or more productsfrom the chemical reaction using spectro-photometric methods known inthe art.

The foregoing description of various embodiments of the invention hasbeen presented for purposes of illustration and description. It is notintended to limit the invention to the precise forms disclosed. Manymodifications, variations and refinements will be apparent topractitioners skilled in the art. For example, the micro-fluidic devicecan have multiple reaction chambers with multiple bubble jet pumpsallowing for the performance of multiple tests one device. Also, themicro-fluidic device can be constructed in a modular fashion to allowparticular features to be selected and assembled by the user.

Elements, characteristics, or acts from one embodiment can be readilyrecombined or substituted with one or more elements, characteristics oracts from other embodiments to form numerous additional embodimentswithin the scope of the invention. Moreover, elements that are shown ordescribed as being combined with other elements, can, in variousembodiments, exist as standalone elements. Hence, the scope of thepresent invention is not limited to the specifics of the describedembodiments, but is instead limited solely by the appended claims.

1. (canceled)
 2. A micro-fluidic device for performing a diagnostic or analytical test, the device comprising: a first chamber configured to be coupled to at least one other micro-fluidic feature and a bubble jet pump; the bubble jet pump structured to control delivery of a fluid from the first chamber to the at least one other micro-fluidic feature by pulling, under vacuum, a selected volume of fluid into the at least one other micro-fluidic feature, wherein another volume of fluid is ejected from a fluidic circuit including the bubble jet vacuum pump so as to create the vacuum.
 3. The device of claim 2, wherein the bubble jet vacuum pump is coupled to the at least one other microfluidic feature by a fluidic channel.
 4. The device of claim 3, wherein the fluidic channel is a capillary.
 5. The device of claim 2, further comprising at least one valve fluidically coupled to at least one of the first chamber, the at least one other chamber or the bubble jet vacuum pump.
 6. The device of claim 2, wherein the first chamber comprises a sample chamber for receiving a sample.
 7. The device of claim 2, wherein the at least one other microfluidic feature comprises a reactant chamber for containing a reactant.
 8. The device of claim 7, wherein the reactant chamber includes a pre-added reactant.
 9. The device of claim 2, wherein the micro-fluidic device comprises a micro-fluidic chip, a micro-fluidic cartridge or a micro-fluidic separation device.
 10. The device of claim 2, wherein the bubble jet vacuum pump includes a heating element.
 11. The device of claim 10, wherein the heating element is a resistive, acoustic, RF, or optical heating element.
 12. The device of claim 2, further comprising a controller electrically coupled to the bubble jet vacuum pump.
 13. The device of claim 12, wherein the controller includes an algorithm for controlling an operation of the micro-fluidic device.
 14. The device of claim 13, wherein the algorithm includes a sequence of valve operations for controlling a sequence of fluid flow between microfluidic features of the device.
 15. The device of claim 2, further comprising a sensor positioned in one of the first chamber, the at least one other microfluidic feature or the bubble jet pump.
 16. The device of claim 15, wherein the sensor is an optical, thermal, pH, gas, sensor.
 17. The device of claim 15, wherein the sensor is configured to detect an analyte, a metabolic analyte, a heme molecule, hematocrit, iron, a drug, an antibody, a bacteria or a virus.
 18. The device of claim 15, wherein the sensor is configured to signal an input to a controller.
 19. The device of claim 2, wherein the at least one other microfluidic feature comprises least one other chamber.
 20. The device of claim 19, wherein the at least one other chamber comprises at least two other chambers.
 21. The device of claim 2, further comprising a port fluidically coupled to one of the first chamber, the at least one other microfluidic feature or the bubble jet pump for the flow of fluid on and off a microfluidic device. 